The goal of this program is to define the pharmacokinetics and metabolism of two drugs commonly implicated in autoimmune reactions in elderly patients and to relate such data to HLA-D locus antigens and to two hypotheses for the molecular mechanism of drug-induced autoimmune disease. SPECIFIC AIMS: 1. To define the pharmacokinetics and metabolism in elderly patients of hydralazine and procainamide in order to establish age-related alterations in drug disposition which might contribute to the subsequent development in these study patients of drug-induced autoimmune disease. Any age-related alterations in drug disposition would also provide data leading to more rational use of these two agents in elderly populations. 2. To perform HLA-D locus typing on study patients who develop drug-induced autoimmune disease in an attempt to establish predictive genetic markers of drug-induced immune response in man. 3. To determine if parent drug or drug metabolite functions as hapten in drug-induced autoimmune disease. This will be accomplished by a) the search for drug-containing auto-antigen in the form of circulating immune complexes or endogenous altered nucleoprotein using isoelectric focusing, gas liquid chromatography and mass spectrometry, and b) the analysis of the specificity and heterogeneity of patients' autoantibody response using a new filter affinity transfer technique. 4. To assess drug affect on T-cell subsets and suppressor cell function using monoclonal anti-alpha and anti-mu antibodies, and the autologous mixed lymphocyte reaction.